Comments

SB290157 has also been reported to have agonist properties at the C3a receptor [25]. The putative chemoattractant receptor termed C5a2 (also known as GPR77, C5L2) binds [125I]C5a with no clear signalling function, but has a putative role opposing inflammatory responses [9,14-15]. Binding to this site may be displaced with the rank order C5a des-Arg (C5)> C5a (C5, P01031) [9,27] while there is controversy over the ability of C3a (C3, P01024) and C3a des Arg (C3, P01024) to compete [17,19-20,27]. C5a2 appears to lack G protein signalling and has been termed a decoy receptor [30]. However, C5a2 does recruit arrestin after ligand binding, which might provide a signaling pathway for this receptor [5,32], and forms heteromers with C5a1. C5a, but not C5a-des Arg, induces upregulation of heteromer formation between complement C5a receptors C5a1 and C5a2 [11]. There are also reports of pro-inflammatory activity of C5a2, mediated by HMGB1, but the signaling pathway that underlies this is currently unclear (reviewed in [24]). More recently, work in T cells has shown that C5a1 and C5a2 act in opposition to each other and that altering the equilibrium between the two receptors, by differential expression or production of C5a-des Arg (which favours C5a2), can affect the final cellular response [4].